The overall goal of this project is to develop a deeper and more comprehensive description and understanding of the natural history and course of dementia of the Alzheimer type (DAT) in severely retarded adults with and without Down syndrome (DS). The development of useful diagnostic procedures for dementia in severely retarded persons will facilitate proper planning of care and improve the quality of life for affected persons. It will also reduce the likelihood of costly errors n diagnosis, treatment and management. The specific aims are: (1) to develop improved methods for the assessment of DAT, (2) to evaluate the psychometric properties of experimental tests of learning, memory and movement-related disorders, (3) to clarify the inconsistencies between longitudinal and retrospective studies. A five-year longitudinal program of research is proposed in which severely retarded adults, varying in age and diagnosis (with DS and without DS), will be evaluated annually. A visual matching-to-sample recognition test, specifically developed for severely retarded persons, will be used as a standard to define clinical status of the participants. A Visual Recognition Span Test, a Table-Top Spatial Location Test, a Large Field Spatial Location Test and a three-part test of movement-related disorders will be evaluated against this standard. A neurological examination will be conducted concurrently with the other examinations to document pre- existing and other relevant clinical conditions affecting the participants. Neuropathological studies will be performed, where possible, during the project period to provide post-mortem confirmation of diagnosis of Alzheimer disease.